Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial

Author:

Haque Tanzina1,Wilkie Gwen M.1,Jones Marie M.1,Higgins Craig D.2,Urquhart Gillian1,Wingate Phoebe1,Burns David1,McAulay Karen1,Turner Marc3,Bellamy Christopher4,Amlot Peter L.5,Kelly Deirdre6,MacGilchrist Alastair7,Gandhi Maher K.8,Swerdlow Anthony J.2,Crawford Dorothy H.1

Affiliation:

1. Clinical and Molecular Virology Laboratory, University of Edinburgh, Edinburgh, United Kingdom;

2. Sir Richard Doll Building, Institute of Cancer Research, Sutton, United Kingdom;

3. Scottish National Blood Transfusion Service, Royal Infirmary, Edinburgh, United Kingdom;

4. Department of Pathology, Royal Infirmary, Edinburgh, United Kingdom;

5. Department of Immunology, Royal Free Hospital and University College Medical School, London, United Kingdom;

6. Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom;

7. Liver Transplant Unit, Edinburgh Royal Infirmary, Edinburgh, United Kingdom,

8. Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia

Abstract

Abstract We present the results of a multicenter clinical trial using Epstein-Barr virus (EBV)–specific cytotoxic T lymphocytes (CTLs) generated from EBV-seropositive blood donors to treat patients with EBV-positive posttransplantation lymphoproliferative disease (PTLD) on the basis of the best HLA match and specific in vitro cytotoxicity. Thirty-three PTLD patients who had failed on conventional therapy were enrolled. No adverse effects of CTL infusions were observed and the response rate (complete or partial) in 33 patients was 64% at 5 weeks and 52% at 6 months. Fourteen patients achieved a complete remission, 3 showed a partial response, and 16 had no response at 6 months (5 died before completing treatment). At 5 weeks, there was a significant trend toward better responses with higher numbers of CD4+ cells in infused CTL lines (P = .001) that were maintained at 6 months (P = .001). Patients receiving CTLs with closer HLA matching responded better at 6 months (P = .048). Female patients responded better than male patients, but the differences were not statistically significant. Our results show that allogeneic CTLs are a safe and rapid therapy for PTLD, bypassing the need to grow CTLs for individual patients. The response rate in this poor prognosis patient group is encouraging.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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